The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

Matos, Leandro Luongo de; Suarez, Eloah Rabello; Theodoro, Therésè Rachell; Trufelli, Damila Cristina; Melo, Carina Mucciolo; Garcia, Larissa Ferraz; Oliveira, Olivia Capela Grimaldi; Matos, Maria Graciela Luongo de; Kanda, Jossi Ledo; Nader, Helena B.; Martins, João Roberto Maciel; Pinhal, Maria Aparecida Silva

doi:10.1371/journal.pone.0141139

Cited by 22 publications

(19 citation statements)

References 44 publications

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“…Several of the 15 non-CGC genes identified have evidence for cancer roles: ANKRD18A in lung cancer 31 , DDX3X and PBRM1 in various cancers 32 , HPSE2 in thyroid carcinoma 33 , MYO5B in gastric cancer 34 . These findings suggest that ExInAtor precision may be better than implied by the analysis of CGC genes alone.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Lanzós

Carlevaro-Fita

Mularoni

et al. 2017

Sci Rep

104

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Long noncoding RNAs (lncRNAs) represent a vast unexplored genetic space that may hold missing drivers of tumourigenesis, but few such “driver lncRNAs” are known. Until now, they have been discovered through changes in expression, leading to problems in distinguishing between causative roles and passenger effects. We here present a different approach for driver lncRNA discovery using mutational patterns in tumour DNA. Our pipeline, ExInAtor, identifies genes with excess load of somatic single nucleotide variants (SNVs) across panels of tumour genomes. Heterogeneity in mutational signatures between cancer types and individuals is accounted for using a simple local trinucleotide background model, which yields high precision and low computational demands. We use ExInAtor to predict drivers from the GENCODE annotation across 1112 entire genomes from 23 cancer types. Using a stratified approach, we identify 15 high-confidence candidates: 9 novel and 6 known cancer-related genes, including MALAT1, NEAT1 and SAMMSON. Both known and novel driver lncRNAs are distinguished by elevated gene length, evolutionary conservation and expression. We have presented a first catalogue of mutated lncRNA genes driving cancer, which will grow and improve with the application of ExInAtor to future tumour genome projects.

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Section: Resultsmentioning

confidence: 99%

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Lanzós

Carlevaro-Fita

Mularoni

et al. 2017

Sci Rep

104

View full text Add to dashboard Cite

show abstract

“…Several of the 15 non-CGC genes identified have evidence for cancer roles: ANKRD18A in lung cancer (30), DDX3X and PBRM1 in various cancers (31), HPSE2 in thyroid carcinoma (32), MYO5B in gastric cancer (33). These findings suggest that ExInAtor precision may be better than implied by the analysis of CGC genes alone.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Lanzós

Carlevaro-Fita

Mularoni

et al. 2016

Preprint

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Long noncoding RNAs (lncRNAs) represent a vast unexplored genetic space that may hold missing drivers 3 of tumourigenesis, but few such "driver lncRNAs" are known. Until now, they have been discovered 4 through changes in expression, leading to problems in distinguishing between causative roles and passenger 5 effects. We here present a different approach for driver lncRNA discovery using mutational patterns in 6 tumour DNA. Our pipeline, ExInAtor, identifies genes with excess load of somatic single nucleotide 7 variants (SNVs) across panels of tumour genomes. Heterogeneity in mutational signatures between cancer 8 types and individuals is accounted for using a simple local trinucleotide background model, which yields 9 high precision and low computational demands. We use ExInAtor to predict drivers from the GENCODE 10 annotation across 1112 entire genomes from 23 cancer types. Using a stratified approach, we identify 15 11 high-confidence candidates: 9 novel and 6 known cancer-related genes, including MALAT1, NEAT1 and 12 SAMMSON. Both known and novel driver lncRNAs are distinguished by elevated gene length, evolutionary 13 conservation and expression. We have presented a first catalogue of mutated lncRNA genes driving cancer, 14 which will grow and improve with the application of ExInAtor to future tumour genome projects.

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“…A study of thyroid carcinoma found that the expression of HPSE2 was increased and tumors showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid [8].…”

Section: Introductionmentioning

confidence: 99%

Expression of heparanase regulates cell proliferation, apoptosis, migration and invasion in vitro in papillary thyroid carcinoma cells with multiple signaling pathways involved

Yang¹,

Zhang²,

Chang³

et al. 2019

Preprint

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Background Heparanase (HPSE) is an endo-β-D-glucuronidase, which is found overexpressed in various human cancers. The purpose of our work was to investigate the possible role of HPSE and the involved signaling molecules in the development of papillary thyroid carcinoma. Methods In this study, the expression plasmid of HPSE and RNA interference with shRNA specific for HPSE were used to elucidate the effects of HPSE on proliferation, apoptosis, migration and invasion in papillary thyroid carcinoma cells of B-CPAP. The probable downstream signaling molecules of HPSE were also explored. Results The results showed that upregulation of HPSE significantly promoted cell proliferation, migration and invasion of B-CPAP cells, and interfered with cell apoptosis. On the contrary, knockdown of HPSE exhibited the opposite effects. Compared with the parental cells, HPSE silencing cells showed attenuated capabilities of proliferation, migration and invasion, yet the apoptotic rate of transfected cells was increased. The activations of various signaling molecules correlated with cell biological behavior were found to be regulated by HPSE upregulation or knockdown. Conclusions Our results suggested that HPSE probably contributed to the progression and metastasis of papillary thyroid carcinoma, which were associated with multiple signaling pathways. HPSE could be a potent molecular target for the therapeutic strategy of papillary thyroid carcinoma.

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The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

Cited by 22 publications

References 44 publications

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features

Expression of heparanase regulates cell proliferation, apoptosis, migration and invasion in vitro in papillary thyroid carcinoma cells with multiple signaling pathways involved

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